BDNF-Dependent Behavioral Sensitization in Hemiparkinsonian Rats

Abstract

A diverse role for BDNF (Brain-derived neurotrophic factor) has been inferred from observations that it is anterogradely transported, released upon neuron depolarization and triggers rapid intracellular signals.1’2 Converging evidence implicates the D3 receptor (D3R) in the physiopathology and treatment of various neuropsychiatrie disorders including Parkinson’s disease, 3, 4 schizophrenia, 5, 6 and drug addiction.7, 8 In a rat model of Parkinson’s disease, obtained by unilateral destruction of dopamine neurons by 6- hydroxydopamine (6-OHDA), D3R expression is decreased in the shell part of nucleus accumbens (AccSh) of the denervated side3, by deprivation of BDNF9 synthesized by dopamine neurons. Repeated administration of levodopa triggers D3R overexpression in the denervated striatum3, which is responsible for the development of behavioral sensitization to levodopa. Progressive enhancement of levodopa-induced rotations are blocked by a preferential D3R antagonist3 and induced by a selective partial D3R agonist.8 Here we show that BDNF is also responsible for induction of D3R overexpression in 6- OHDA-lesioned rats, and thereby for behavioral sensitization.